Renal dysfunction or failure and, in particular, end-stage renal disease, causes the body to lose the ability to remove water and minerals and excrete harmful metabolites, maintain acid-base balance and control electrolyte and mineral concentrations within physiological ranges. Toxic uremic waste metabolites including urea, creatinine and uric acid accumulate in the body's tissues which can result in a person's death if the filtration function of the kidney is not replaced.
Dialysis is commonly used to replace kidney function by removing these waste toxins and excess water. In one type of dialysis treatment—hemodialysis—toxins are filtered from a patient's blood externally in a hemodialysis machine. Blood passes from the patient through a dialyzer separated by a semi-permeable membrane from a large volume of externally-supplied dialysate. The waste and toxins dialyze out of the blood through the semi-permeable membrane into the dialysate, which is then discarded. Hemodialysis treatment typically lasts several hours and must be performed under medical supervision three or four times a week, requirements that significantly decrease a patient's autonomy and quality of life. Also, since hemodialysis is performed periodically instead of continuously, the patient's condition and general well-being tend to be poor both immediately before (when toxin levels are high) and after (when electrolytes are imbalanced) hemodialysis, resulting in the patient having symptoms that range from nausea and vomiting to edema.
Peritoneal dialysis is another type of dialysis treatment used to replace kidney function in which sterile, pyrogen-free dialysis solution is infused into the patient's peritoneal cavity. The peritoneal membrane serves as a natural dialyzer and toxic uremic waste metabolites and various ions diffuse from the patient's bloodstream across the membrane into the dialysis solution via an osmotic gradient. The dialysis solution is removed, discarded and replaced with fresh dialysis solution on a semi-continuous or continuous basis. Although not all peritoneal dialysis systems require medical supervision in a treatment center, draining, discarding and replacing the large volumes of solution needed for peritoneal dialysis is still inconvenient, unwieldy and expensive.
To address this problem, devices have been designed that reconstitute used dialysate from hemodialysis and/or peritoneal dialysis as opposed to discarding it. The solution can be regenerated in a machine employing a device that eliminates urea from the solution. For example, the original Redy® (REcirculating DYalysis) Sorbent System (Blumenkrantz et al., Artif Organs 3(3):230-236, 1978) consists of a sorbent cartridge having five layers through which dialysate solution containing uremic waste metabolites flows in order to be regenerated. The spent dialysate flows through a purification layer that removes heavy metals (i.e., copper and lead) and oxidants (i.e., chlorine and chloramine), an aluminum oxide layer bound to urease which degrades the urea in the dialysate into ammonium carbonate, a zirconium phosphate layer that adsorbs the ammonium ions produced from urea degradation along with other cations (i.e., potassium, magnesium and calcium), a hydrated zirconium oxide layer that exchanges phosphate and other anions (i.e., fluoride) for acetate and an activated carbon layer that absorbs other organic compounds (i.e., creatinine and uric acid).
Typically, the ion exchange resins used in devices such as the Redy® Sorbent System absorb not only the urea degradation products, but also essential ions like calcium and magnesium that have diffused into the peritoneal dialysis solution. These ions must then be rapidly replaced in the patient; however, there currently is no easy or convenient mechanism to do so. Further, although hemodialysis and peritoneal dialysis dialysate can be regenerated, no device has yet been devised that both operates continuously, clears uremic waste metabolites effectively and is small enough and/or weighs little enough to actually be comfortably worn by a patient at all times.
There is a need for a dialysis device that is safe and effective and that significantly improves a patient's quality of life over current devices and methods. What is required is a dialysis device that operates regularly enough such that the patient does not feel unwell for significant periods of time and one that does not consume large blocks of the patient's time, require medical supervision, require volumes of dialysate so large that the patient must practicably remain stationary, nor remove essential ions and minerals from the patient that then must be replaced externally. It would also be advantageous for the system to be safe enough for a patient to wear continuously and perform normal activities with little worry; that is, a system that does not involve the filtration of blood (e.g., hemodialysis), as a malfunction or disconnect within the blood circulation system could easily occur and result in rapid blood loss and death. Thus, there would be a great benefit to a dialysis system that truly allows a patient to function independently. Hence, a peritoneal dialysis device that is small enough to be comfortably worn by a patient continuously during daily activities and contains a regenerative device that is capable of reconstituting the dialysis solution without also removing essential ions from the patient.